Effect of COX-2 and EGFR Suppression on Molecular Markers of Angiogenesis and Proliferation in Squamous Cell Carcinoma of Oral Cavity - Prospective Randomized Study

NCT02748707 | Unknown Phase 2 DMC

• 1 other identifier: 830
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II randomized clinical trial to study the effect of COX-2 inhibitor Celecoxib and EGFR tyrosine kinase inhibitor Erlotinib alone or in combination on molecular markers of apoptosis and angiogenesis.

Conditions

Oral Squamous Cell Carcinoma; Carcinoma of Buccal Mucosa; Tongue Cancers; Head and Neck Cancers

Outcome Measures

Primary Outcomes (1)

• Change in expression of selected biomarkers in tissue samples, assessed by immunohistochemistry (IHC) and PCR

  Tumor tissues will be collected and stored before and after treatment. The pre and post treatment tumor tissue will be analyzed semiquantitatively by immunohistochemistry for the levels of COX-2 (Cyclooxygenase-2), EGFR (epidermal growth factor receptor), TP53 (Tumor protein 53) and VEGF (Vascular endothelial growth factor) expression. Their baseline gene expression and fold change after treatment will be assessed by quantitative real time polymerase chain reaction (qPCR) using facility at TMC.

  baseline and 21 days

Secondary Outcomes (1)

• Clinical and radiological Change in tumor size and appearance

  baseline and 21 days

Other Outcomes (1)

• Disease free survival

  Date of randomization to date of disease recurrence, or appearance of a new primary or death.

Study Arms (4)

Arm 1

EXPERIMENTAL

Celecoxib 200mg twice daily for 21 days

Drug: Arm1

Arm 2

EXPERIMENTAL

Erlotinib 150 mg once daily for 21 days

Drug: Arm 2

Arm 3

EXPERIMENTAL

Celecoxib 200 mg twice daily for 21 days and Erlotinib 150 mg once daily for 21 days

Drug: Arm 3

Arm 4

SHAM COMPARATOR

Control group with no drug

Other: Arm 4

Interventions

Arm1 DRUG

Drug (Celecoxib as 200mg twice daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery

Also known as: Celecoxib

Arm 1

Arm 2 DRUG

Drug (ERLOTINIB 150 mg daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery

Also known as: Erlotinib

Arm 2

Arm 3 DRUG

Drugs (Celecoxib 200mg twice daily and Erlotinib 150mg once daily) given orally for 21 days after confirmation by biopsy and before definitive treatment by surgery

Also known as: Celecoxib + Erlotinib

Arm 3

Arm 4 OTHER

Patients randomized to this arm will be observed for 21 days before definitive treatment by surgery.Having a control group is ethically justifiable because the average waiting time in our hospital prior to definitive treatment is 30 days after diagnosis.

Also known as: Observation

Arm 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with squamous cell carcinoma of oral cavity (T2-T4, N1-2, M0) and are candidates for first line curative surgical treatment and are able to swallow orally, preoperatively.
• Patients must be at least 18 years of age.
• All patients must sign an informed consent before enrolling in study.
• Patients must be able and willing to return to the clinic at appropriately scheduled intervals.
• No use of systemic steroids or topical oral steroid preparations within three months. (Topical nasal steroid sprays or cutaneous preparations with minimal systemic absorption for nasal or dermatologic disorders are allowed).
• Premenopausal women must be using adequate birth control methods and have a negative pregnancy test prior to entry.
• Karnofsky Performance Score above 80.
• The subject is willing and able to fully participate for the duration of the study.
• If applicable, the subject has been counseled on smoking cessation.
• The subject meets the following laboratory eligibility criteria during a time not to exceed 4 weeks prior to randomization.
• Hemoglobin level above 10gm/dl, the lower limit of normal.
• WBC count \> 3,000 mm3.
• Platelets count \> 100,000 m3.
• Total bilirubin, AST (Aspartate Aminotransferase) and ALT (Alanine transaminase) ≤ 2 x ULN.
• Serum creatinine ≤ 2 x Upper limit of Normal (ULN)

You may not qualify if:

• \. History of cardiovascular co morbidities 2. Patients with previous history of head and neck cancers 3. Recent massive gastrointestinal hemorrhage 4. An on-going unmanaged serious infectious disease or major metabolic disorder 5. Neutrophil count of \<1 x 109 per liter or platelet count of \< 75 x 109 per liter at study entry, 6. Bilirubin at \>1.5-fold above the upper limit of normal, and 7. Kidney failure (Glomerular filtration rate of \<40 mL/min). 8. Pregnant women 9. Use other nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids within 2 weeks prior to initial clinical evaluation 10. The subject is, in the opinion of the Institutional Principal Investigator, not an appropriate candidate for study participation.

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (1)

Tata Memorial Center (TMC)

Mumbai, Maharashtra, 400012, India

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms; Head and Neck Neoplasms

Interventions

26S proteasome non-ATPase regulatory subunit 13; Celecoxib; DMAC2L protein, human; Erlotinib Hydrochloride; Observation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Mouth Neoplasms; Mouth Diseases; Stomatognathic Diseases; Tongue Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Methods; Investigative Techniques

Study Officials

• Sudhir V Nair, MBBS, MS,MCh

  Tata Memorial Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: April 22, 2016
• Study Start: August 18, 2015
• Primary Completion: February 12, 2018
• Study Completion: April 1, 2023
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)